The human immunodeficiency virus (HIV) is a pathogenic retrovirus (Varmus, H. (1988) “RETROVIRUSES,” Science 240:1427-1439; Cowley S. (2001) “THE BIOLOGY OF HIV INFECTION” Lepr Rev. 72(2):212-20). It is the causative agent of acquired immune deficiency syndrome (AIDS) and related disorders (Gallo, R. C. et al. (1983) “Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS),” Science 220(4599):865-7; Barre-Sinoussi, F. et al. “ISOLATION OF A T-LYMPHOTROPIC RETROVIRUS FROM A PATIENT AT RISK FOR ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS),” (1983) Science 220:868-870; Gallo, R. et al. (1984) “FREQUENT DETECTION AND ISOLATION OF CYTOPATHIC RETROVIRUSES (HTLV-III) FROM PATIENTS WITH AIDS AND AT RISK FOR AIDS,” Science 224:500-503; Teich, N. et al. (1984) “RNA TUMOR VIRUSES,” Weiss, R. et al. (eds.) Cold Spring Harbor Press (NY) pp. 949-956). HIV acts to compromise the immune system of infected individuals by targeting and infecting the CD4+ T lymphocytes that would otherwise be the major proponents of the recipient's cellular immune system response (Dalgleish, A. et al. (1984) “THE CD4 (T4) ANTIGEN IS AN ESSENTIAL COMPONENT OF THE RECEPTOR FOR THE AIDS RETROVIRUS,” Nature 312: 767-768, Maddon et al. (1986) “THE T4 GENE ENCODES THE AIDS VIRUS RECEPTOR AND IS EXPRESSED IN THE IMMUNE SYSTEM AND THE BRAIN,” Cell 47:333-348; McDougal, J. S. et al. (1986) “BINDING OF HTLV-III/LAV TO T4+ T CELLS BY A COMPLEX OF THE 110K VIRAL PROTEIN AND THE T4 MOLECULE,” Science 231:382-385). HIV infection is pandemic and HIV-associated diseases represent a major world health problem.
HIV infection is believed to occur through the fusion of viral-cell and cell-cell membranes. This process is mediated by the gp41 and gp120 HIV env proteins and the cellular CD4 protein. Following binding of gp120 to CD4, a conformational change occurs in the gp120/gp41 complex. This change leads to the insertion of the gp41 protein into the target membrane and ultimately to membrane fusion.